The production of two daughter cells from one parent cell is a complex yet elegant process that is essential for the normal growth and maintenance healthy tissue. This process, known as the cell cycle, involves a series of sequential steps termed G1 (gap 1), S (synthesis), G2 (gap 2), and M (mitosis). S phase is characterized by a doubling of a parent cell's chromosomal DNA. In M phase, a cell precisely halves the doubled DNA and then divides itself into two daughter cells in a process termed cytokinesis. G1 is the period following M phase but before S phase during which time the cell prepares for replication of its chromosomal DNA. G2 is the period between S phase and M phase during which the cell prepares for mitosis and cytokinesis.
Several distinct families of cytoplasmic proteins are known to regulate passage of cells through the various phases of the cell cycle. Among the better characterized of these is the cyclin family of proteins. The cyclin family is subdivided into three groups according to the phase of the cell cycle in which they act, i.e., the G1-, S-, and M-phase cyclins. The amount of a particular cyclin expressed by a cell fluctuates through the progression of the cell cycle. For example, G1 cyclin levels rise during the G1 phase and S cyclin levels rise during the S phase.
A second family of cell cycle regulatory proteins is the cyclin-dependent kinase (CDK) family. Proteins in the CDK family are also classified in one of three groups, i.e., G1-, S-, and M-phase CDKs. These proteins are capable of phosphorylating a variety of protein substrates that control various processes at different phases of the cell cycle. Cyclins are also known to physically interact with CDKs in a process that leads to modulatation of CDK kinase activity. For example, M-phase CDK and M-cyclins complex with each other to form an M-phase promoting factor. This factor is instrumental in initiating events leading up to the metaphase stage of mitosis, including assembly of the mitotic spindle, condensation of the chromosomes and breakdown of the nuclear envelope.
A third recognized regulator of the cell cycle is the retinoblastoma protein (pRb). This protein is known as a growth suppressor gene because it can prevent the progression of a cell towards the S phase. Recent research has indicated that pRb plays a major role in regulation of the cell cycle, differentiation, and apoptosis. This protein may cooperate with another protein termed p53 which is known to prevent the division of cells with abnormal DNA and force abnormal cells to self-destruct through apoptosis.
From the foregoing, it is apparent that cell division is an extraordinarily complex and tightly-orchestrated event, with each phase of the cell cycle in itself comprising a complicated series of cellular and molecular events. Unfortunately, many of the molecular bases for these events remain poorly understood. Discovery and characterization of new molecules involved in cell cycle regulation should lead to more complete understanding of this process.